Transdermal drug delivery system of strychnine, brucine, securinine and their salts

ABSTRACT

Strychnine, brucine (A) and securinine (B) are a group of natural drugs for central excitation. Because their oral dose or injection dose is close to the half lethal dose, the drugs, with a great toxic side effect, may be lethal if improperly used. The invention is characterized by using the transdermal drug delivery system as a substitute for the oral or injection dosage form to directly act on the local nervous system through the skin, avoiding the toxic side effect caused by drugs directly entering the blood circulating system. The dose through cutaneous absorption is far lower than the oral or injection dose, so it has a much higher safety and a longer acting effect. The transdermal drug delivery system is useful for the treatment of central or peripheral neural paralysis and other nervous system related diseases.

FIELD OF THE INVENTION

The present invention relates to pharmacology of strychnine, brucine andsecurinine.

BACKGROUND OF THE INVENTION

There is a lack of specific drugs for the treatment of central orperipheral neural paralysis and neural dysfunction. From a traditionalChinese viewpoint, “every sort of drug has certain toxicity”. Intraditional Chinese medicine, poisonous plant drugs or mineral drugs areoften used to treat many difficult and complicated cases of disease,receiving a noticeable curative effect. For example, Nuxvomica andsecurinega suffruticosa are capable of treating the above diseases.

Strychnine, brucine and securinine extracted from those plants provedpotency to treat for the above-mentioned diseases. At present,strychnine and securinine are used as drug only in China.

Whether strychnine and securinine are taken orally or injected, the drugdelivery dose is very close to the toxic dose, so it is very unsafe touse them like this. But a change in the route of medication may make itpossible to improve the safety and reduce side effects, which will leadto wider use of those drugs.

SUMMARY OF THE INVENTION

1. Pharmacology of Strychnine, Brucine and Securinine

The natural products involved in the invention are strychnine, brucineand securinine, whose chemical structures are:

X═H—, strychnine securinineX═CH₃O—, brucine

Strychnine, brucine and securinine can all excite the spinal reflexfunction, respiratory center, vagus nerve center, coughing center andvasomotor center. They also can strengthen the excitation process of thecerebral cortex, making the patients in an inhibitory state come totheir senses, and improve the functions of the sense organs of taste,touch, hearing and sight.

2. Toxicity of Strychnine, Brucine and Securinine

Excessive strychnine, brucine and securinine can all make the spinalreflex excitation significantly sthenic, causing tetanic spasm and evendeath from asphyxia due to tetanic contraction of the respiratorymuscle.

3 Feasibility of Transdermal Drug

Transdermal drug delivery system can help avoid toxic side effects ofthe above drugs, but the problem is whether it can use it to achieve thesame curative effect. There is a direct correlation between the curativeeffect of transdermal drug delivery. system and the type of disease. Theneurological disease that differs from the viral disease can be treatedby stimulating the local nerve, which has an action on the focus throughnerve conduction, similar to acupuncture and moxibustion used as thetreatment of neurological disease in traditional Chinese medicine.Strychnine, brucine and securinine are drugs for the treatment ofneurological disease and they also can achieve the drug delivery effectby acting on local nerves of the human body just like “moxa treatment”in Chinese acupuncture and moxibustion.

The key of this invention is that strychnine, brucine and securinine invaseline is easy to infiltrate into skin. Vaseline can keep strychnine,bucine and securinine better solubility in vaseline, and it can keepboth skin moisture and skin pores bigger. The drug effect of strychnine,brucine/ and securinine in vaseline will be proved.

4. Potency and Safety of Transdermal Drug

1% strychnine ointment is applied to the skin above the facial nervesuffering from central or peripheral facial palsy at the relatedacupuncture points once a day. Those who suffer from Bell's palsy of 1to 90 day duration need 1-20 day course of treatment. Those who sufferfrom facial palsy caused by apoplexy need about 20-40 day duration fortreatment. The total effective rate, curative ratio and effective rateare all higher than with acupuncture and moxibustion or Westernmedicine. Even one who has a course of disease of more than 7 years hasalso achieved a very good curative effect. The external applicationexperiment involved volunteers showed no skin allergic reaction or otherside effects. So transdermal drug is both safe and potency drug.

5 Preparation of Transdermal Drug

Strychnine, brucine and securinine infiltrate through the skin into thebody more easily than their salts. They all have certain solubility invaseline. Vaseline that has a certain action of promoting retention ofskin moisture can help increase the rate at which. they infiltratethrough the skin. It is easy to make them into ointments or patches.

Some paralysis diseases are related to viral infection. The addition ofantibiotics, antifungals and other drugs can help treat for the abovediseases at the acute stage, so it is necessary to prepare thetransdermal drug with of antibiotics or antifungals.

The infiltration rate of strychnine, brucine and securinine in vaselineis enough, so it is not necessary to use any promoter. Vaseline is agood promoter actually.

The transdermal drug refers to the ointment, plaster and patch. Thetransdermal drug is easy to be prepared.

6. Method of Application of Transdermal Drug

In order to achieve a better effect of transdermal drug, it is worthrecommending the acupuncture point selected in the Chinese techniques ofacupuncture and moxibustion. It requires selecting different parts oracupuncture points of the body based on different diseases. For example,to treat for facial palsy, the transdermal drug should be applied toFengchi, Xiaguan, Taiyang, Jiache and other related acupuncture points.To treat sexual disorder and peripheral non-cream disease, thetransdermal drug should be applied to Mingmen, Shenyu, Guanyuan, Baihuiand other related acupuncture points.

7. Diseases that Can be Treated with Transdermal Drug of Strychnine,Brucine and Securinine in Vaseline.

The transdermal drug can be used to treat for central or peripheralneural paralysis and neural dysfunction, such as: facial paralysis,hemiplegia, general paralysis, respiratory muscle paralysis, spinalincomplete paralysis, incomplete sphincter, relaxation, prolapse of thepenis, Green-Barley syndrome, anal prolapse, peripheral non-creamdisease, sexual disorder, sequela of poliomyelitis, myasthenia gravisand amblyopia, postnatal balk anemia.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

1. Preparation of Ointments

Experiment 1

2-30 mg strychnine and 3 g vaseline are stirred in 50° C. about 10minutes, which is then put in a package.

2. Preparation of Plaster

Experiment 2

Some of Vaseline containing strychnine, brucine or securinine is appliedto the center of a piece of cloth with mucilage glue around the sides.

Industrial Applicability

The preparation for external application is more potency, safe andconvenient than the that for oral or injection administration,susceptible of industrial production.

1. The transdermal drug of strychnine, brucine, securinine or theirmixtures with or without antibiotics or antifungals in vaseline for thetreatment of central or peripheral neural paralysis or neuraldysfunction.
 2. According to claim 1, the transdermal drug containsstrychnine, brucine, securinine or their mixture respectively. 3.According to claim 1, the transdermal drug contains vaseline. 4.According to claim 1, the transdermal drug includes ointment, plasterand patch.
 5. According to claim 1, the transdermal drug can containantibiotics or antifungals for treatment of some diseases.
 6. Accordingto claim 1, the transdermal drug can treat for central or peripheralneural paralysis and neural dysfunction, such as: facial paralysis,hemiplegia, general paralysis, respiratory muscle paralysis, spinalincomplete paralysis, incomplete sphincter relaxation, prolapse of thepenis, Green-Barley syndrome, anal prolapse, peripheral non-creamdisease, sexual disorder, sequela of poliomyelitis, myasthenia gravisand amblyopia, postnatal balk anemia.